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Heavy metals accumulate in biological tissue and produce confounding effects in long-term studies

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Conditions include alcoholic liver disease, viral hepatitis, cirrhosis, and primary or metastatic liver cancer Renal dysfunction : Impaired kidney function reduces B12 elimination, causing accumulation even with normal intake Haematological conditions : Myeloproliferative neoplasms, chronic myeloid leukaemia, polycythaemia vera, and hypereosinophilic syndrome increase transcobalamin production, elevating total serum B12 Laboratory interference : Macro-B12 (immunoglobulin-bound B12) and assay interference can cause spuriously elevated results without true excess In clinical practice, unexplained hypercobalaminaemia should prompt investigation for underlying disease, particularly in patients without obvious supplementation history

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